The enantioselective functionalization of prochiral C—H bonds represents a highly efficient transformation by installing both valuable oxidized functionality and absolute stereochemistry in a single step. Asymmetric allylic C—H oxidations have been pursued over the last five decades; copper catalyzed Kharasch-Sosnovsky reactions have achieved satisfactory enantiomeric excesses, however only with symmetrical, cyclic olefins under synthetically undesirable conditions (excess equivalents of olefin, days at cryogenic temperatures) (Scheme 1A). Palladium has shown a broad scope in enantioselective C—H desymmetrizations and kinetic resolutions, however Pd-catalyzed asymmetric allylic C—H functionalizations have been achieved hereto with only modest levels of asymmetric induction. Additionally, Pd-catalyzed asymmetric C—H to C—O bond-forming reactions are rare.
Due to the ubiquity of C—N bonds in natural products and pharmaceuticals, the cross-coupling of amines with hydrocarbons under fragment coupling conditions (1 equivalent) stands to significantly impacted chemical synthesis. Whereas significant progress has been made in cross-couplings of amines with aryl halides to form C(sp2)-N bonds, the development of analogous C(sp3)-N coupling reactions remains an elusive goal.
Site, chemo- and stereoselective Pd(II)-catalyzed reactions for intermolecular allylic C—H aminations of α-olefins are well-precedented; however, all require use of N-tosyl carbamate nucleophiles. These reactions proceed via near ligandless conditions (e.g. reversibly coordinating sulfoxide ligands) that may lead to catalyst deactivation in the presence of more basic and coordinating nitrogen nucleophiles.
Accordingly, there is a need for transition metal complexes that can catalytically activate an allylic C—H bond under simple reaction conditions to provide C(sp3)-heteroatom functionalized products with efficient regio- and stereoselective catalyst-control.